A major concern in the neurobiology of aging is the progressive decline in the ability to learn and remember that accompanies old age. Despite their importance, surprisingly little is known about the synaptic changes and cellular mechanisms that underlie these age-impaired learning and memory processes. The research outlined in this proposal is designed to focus on this important problem by examining the synaptic correlates of specific age-dependent learning and memory deficits in a model system, the marine mollusc Aplysia californica. Aplysia can be cultured in the laboratory, has a short-life span, and has identified nerve cells of known behavioral function. Recently my colleagues and I have examined the effect of age on the acquisition and retention of two simple forms of non-associative learning: sensitization and habituation in the gill- and siphon-withdrawal reflex. Preliminary results suggest that the acquisition of one form of learning (sensitization) and the long-term memory of another (habituation) are significantly impaired in old animals. Since the critical synapses and aspects of the mechanisms that underlie both forms of learning are known it is now possible to use the gill- and siphon-withdrawal reflex as a model system in which to examine in detail the cellular basis of these age-dependent impairments in learning and memory. I will approach this study on two levels: First I will carry out an analysis of the locus and nature of synaptic changes that parallel the impaired acquisition of sensitization and the altered retention of habituation. Having established this correlation, I will next carry out an analysis of the causal cellular and molecular mechanisms that produce the age-dependent deficits in learning and memory.